One of the fundamental problems in neurobiology is to understand the cellular and molecular events underlying learning and memory. Considerable progress has been made in understanding the neural basis of simple forms of learning in the marine mollusk, Aplysia, through the study of two simple defensive withdrawal reflexes, tail siphon withdrawal and gill siphon withdrawal. These reflexes can be modified by sensitization, a simple form of non-associative learning in which the behavioral response to a mild stimulus is enhanced following the presentation of another, usually noxious, stimulus. Previous studies suggest that one general correlate of sensitization is the modification of neuronal structure. However, this assumption may be oversimplified. Preliminary studies suggest that there may be multiple forms of long-term sensitization, and that morphological changes are only induced by the more present forms of this memory. The specific aims of this research project are: 1) to determine the time course of long-term sensitization in the tail induced siphon withdrawal reflex; 2) to determine the conditions that induce a form of long-term sensitization associated with morphological changes; and 3) to examine the functional role of neuronal outgrowth in long-term sensitization. The effects of various training protocols on both the behavioral response of the reflex, and on the morphology of the sensory neurons mediating this response will be analyzed. Changes in neuronal morphology will be analyzed using 3-D reconstructions of the neuronal structure. In addition, we will use confocal microscopy to examine whether neuronal outgrowth is contributing to the behavioral response by strengthening pre-existing connections to motor neurons, or by adding new connections to the neuronal circuitry underlying the response. Through the quantitative analysis of neuronal morphology we hope to provide a more complete framework for a structural model of learning and memory.